Khorana was an exceptional visionary

On November, 9, 2011 the world witnessed the silent departure of a great scientific revolutionary, Prof Har Gobind Khorana, a man renowned for cracking the code to life.
Born in a small village in Punjab (now in Pakistan), Har Gobind was the youngest of five siblings. Despite poor financial condition, his father’s desire to educate his children laid the foundation for Khorana’s glorious academic career. As Khorana said, “Although poor, my father was dedicated to educating his children and we were practically the only literate family in the village inhabited by about 100 people.”

After being homeschooled, Khorana went to Punjab University, Lahore, for graduation. A shy village lad applied for admission in two departments, English literature and Chemistry, but destiny had something else in store for him and despite restricted admittance and his failure to attend the qualifying interview, Khorana managed to get admitted into the Chemistry department.

Driven by destiny

After postgraduation from the same university in 1945, he was awarded a studentship by the government to study insecticides and fungicides in England.

But destiny drove him to the Chemistry department of Liverpool University where he was trained as an organic chemist during his PhD, following which he went to the Eidgenössische Technische Hochschule in Zurich, Switzerland for postdoctoral studies to work with Vladimir Prelog, a Croatian chemist and a Nobel prize winner in chemistry. During his stay at the Swiss institute, he was fascinated towards carbodiimides, chemical compounds formed after removal of water molecules from urea, which formed an essential part of his research work in later years.

After completing higher education abroad, Khorana returned to India, but the Partition-affected country did not have anything to offer him and subsequent course of events took him back to Cambridge University where he resumed his research career as a postdoctoral fellow in Alexander Todd’s laboratory, who was at the climax of solving the structures of nucleic acids, the main components of our genes.

His stay at Cambridge allowed him to witness some of the greatest discoveries in science, from sequencing of the first protein-insulin by Frederick Sanger to determination of the way how DNA looks by Watson and Crick. After spending two years in Cambridge, he went to the University of British Columbia, Vancouver, in 1952 where he began his pioneering studies on nucleic acids with inspiration from Dr Gordon M Shrum. That year he married Esther Elizabeth Sibler, who became a supporting pillar.

In 1960, he joined the Institute for Enzyme Research at the University of Wisconsin–Madison, finally becoming the Alfred Sloan Professor of Biology and Chemistry at the Massachusetts Institute of Technology in 1970 till his retirement in 2007.

The 1960s have been regarded as the golden era of molecular biology and Khorana’s own contribution in the development of this field as an independent discipline is exceptionally outstanding.  He began his scientific trysts by synthesising polymers of nucleic acids or oligonucleotides using carbodiimides and making short chains of amino acids (the building blocks of proteins) from them by a process of in vitro translation. His diligence bore fruit and he became the first person to synthesise oligonucleotides and construct the first artificial gene.  In 1961 he made another breakthrough by synthesising coenzyme A, a small molecule of biological relevance that participates in over 9 per cent of all chemical reactions occurring within a living cell. He even devised a method to make several copies of DNA, which he termed “Repair Synthesis.”

It was during this time that he deciphered the biological language of genes and demonstrated to the world how genes code for proteins that make life. This historic invention was duly recognised when he was awarded the Nobel Prize for medicine in 1968 along with Marshall W Nirenberg and Robert W Holley.

Following the discovery of the genetic code his interests radically shifted and since then he worked on mechanisms governing conversion of light energy to chemical energy by proteins bacteriorhodopsin and rhodopsin, a biological pigment of the retina and had about 400 scientific publications to his name in leading journals. His first student, Michael Smith, was a recipient of the 1993 Nobel Prize in Chemistry for devising site-directed mutagenesis, a method of manipulating DNA.

Apart from the Nobel, Khorana was honoured with several other prestigious awards. The remarkable contributions of the man who laid the stepping stone for the creation of artificial life and raised hope for treatment of genetic disorders with synthetic DNA will  forever be cherished and we will always remain indebted for his endowments to us.

(The writer is Director, National Institute of Immunology)